Ganoderma tsugae extracts inhibit colorectal cancer cell growth via G(2)/M cell cycle arrest.
BACKGROUND
Ganoderma, known as Lingzhi or Reishi, has been traditionally administered throughout Asia for centuries as a cancer treatment and for other medicinal purposes.


OBJECTIVE
To investigate the inhibitory activity and explore the molecular mechanisms of anti-tumor effect on colorectal cancer cells in vitro and in vivo as well as to test the side effects of Ganoderma tsugae.


METHODS
Methanol fraction was obtained from dried fruiting bodies of Ganoderma. TLC and HPLC were performed to differentiate and confirm the identification of different species as well as to quantify the bioactive molecules in methanol extracts of Ganoderma species. MTT and Trypan blue exclusion assay as well as tumorigenesis study were used to assess the anti-tumor effect in vitro and in vivo. Using flow cytometry and Western Blots, we examined further the molecular mechanisms of anti-tumor effect. Finally, biochemical and hematological profiles and pathological examinations were used to evaluate the safety.


RESULTS
The Ganoderma tsugae extracts inhibit colorectal cancer cell proliferation caused by accumulating cells in G(2)/M phase, and it may be through downregulation of cyclin A and B1 and upregulation of p21 and p27. Tumorigenesis study in nude mice revealed the extracts caused tumor shrinkage. Additionally, safety assay showed Ganoderma tsugae extracts caused no significant side effects in an animal model.


CONCLUSIONS
This study provides molecular evidence that Ganoderma tsugae extracts exert anti-tumor effects both in vitro and in vivo on colorectal adenocarcinoma cells by inducing G(2)/M cell cycle arrest. More importantly, no significant physiological changes resulting from treatment with Ganoderma tsugae extracts were observed in the animal model. Therefore, these data provide new insights into the possible therapeutic use of Ganoderma tsugae for treating colorectal cancer.
Hsu
Shih-Chung
SC
Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan; Kang-Ning Junior College of Medical Care and Management, Taipei, Taiwan.
Ou
Chien-Chih
CC
Li
Jhy-Wei
JW
Chuang
Tzu-Chao
TC
Kuo
Han-Pon
HP
Liu
Jah-Yao
JY
Chen
Chin-Shiang
CS
Lin
Song-Chow
SC
Su
Ching-Hua
CH
Kao
Ming-Ching
MC
D000230:Adenocarcinoma / Q000188:drug therapy; D000704:Analysis of Variance; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D032902:Ganoderma / Q000737:chemistry*; D006801:Humans; D008516:Medicine, Chinese Traditional / Q000379:methods; D051379:Mice; D008819:Mice, Nude; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use*; D013624:Taiwan
D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts